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Flumazenil and seizures
ever, none of these trauma patients received more than supportive care. The ingestant profile differed from previous studies. Though many of these ingestants may have affected initial physical evaluation, subsequent care was not altered. More directed drug screening would identify those drugs requiring specific intervention.
7
Flumazenil and Seizures
D Seger / Vanderbilt University School of Medicine, Section of Surgical Sciences, Division of Trauma, Nashville, Tennessee Flumazenil, a specific benzodiazepine (BZDP) antagonist, is a safe and effective means of reversing central nervous system depressant effects of BZDP. However, clinical trials indicated that reversal of BZDP activity in mixed intoxications with tricyclic antidepressants present may induce seizures. The seizure potential of flumazenil in the presence of tricyclic antidepressants was addressed in an animal model. Twelve pigs {mean weight, 18.7 _+ 4.3 kg) were anesthetized with halothane and nitrous oxide, intubated, and mechanically ventilated. A continuous infusion of nortriptyline was administered until the QRS complex widened to 120 ms. The pigs were divided into three groups of four. In group 1, 15 mg/kg of diazepam was intravenously administered, followed ten minutes later by 5 mg/kg flumazenil. In group 2, 5 mg/kg flumazenil was the sole drug administered. No seizures were observed in group 1 or 2. In group 3, 15 mg/kg diazepam was administered. One animal in this group had seizures. Although the groups are small, these preliminary data indicate that flumazenil does not induce seizures in the presence of tricyclic antidepressants.
8
Fatal Outcome Following Carbon Monoxide Exposure in Pregnancy; A Prospective MulUcenter Study
G Koren, T Sharav, the collaborative group. The Motherisk Program, The Hospital for Sick Children, Toronto, Canada Carbon monoxide (CO) exposure in pregnancy has been reported in more than 45 cases of severe poisoning, mainly with matemal coma, to cause fetal death or permanent central nervous system damage. However, most cases of CO poisoning are not of grades 46, but rather 1-2, without loss of maternal consciousness. No information on fetal outcome after mild-to-moderate CO poisoning has been reported, and therefore counseling of the affected family during pregnancy was not possible. In this multicenter study we have prospectively collected 40 cases, of whom fetal outcome is known in 32, with follow-up of at least one year. These cases were caused by malfunction of furnaces (19), water heaters {six}, and car fumes {seven}. All 25 pregnancies {two sets of twins} with grade 1-2 poisoning resulted in physically and developmentally normal babies up to 1 year of age. Conversely, three of five grade 4-5 poisoning resulted in serious adverse outcome (one maternal and fetal death, one fetal death, and one cerebral palsy with computed tomography scan consistent with severe asphyxia despite uneventful delivery} (P < .001 in Fisher's exact test). An additional woman with grade 5 chose to terminate pregnancy based on information given to her in Motherisk. The two cases of normal outcome after grade 4-5 pois0ning were treated with hyperbaric oxygen whereas adverse fetal effects followed high-flow oxygen. Birth weight was not affected by the time of exposure during gestation. Our data suggest that grades 1-2 CO poisoning are not associated with major fetal damage, whereas following grades 4-5 the likelihood of fetal damage is high and the family should consider termination of pregnancy.
19:6June 1990
Annals of
9
2,3-Dimercaptosuccinic Acid (DMSA) Versus N.AcetyI.Penicillamine (NAP) for the Treatment of Elemental Mercury Toxicity
R Bluhm, RG Bobbitt, JF Bonfiglio, RA Branch, C Sarzen, L Welch, AJJ Wood, AJ Heath / Departments of Medicine and Psychiatry, Vanderbilt University, Nashville, Tennessee Thirty-five patients exposed to elemental mercury vapor during an industrial accident were followed for more than six months. Respiratory symptoms developed within a few days of exposure. Dysuria and ejaculatory pain were noted in six patients. Central nervous system symptoms of headache, memory impairment, and hostility persisted for months. Twenty-three patients were chelated. Twelve were admitted between 73 and 116 days after exposure for a comparative study of DMSA {30 mg/kg/day} and NAP {250 mg every six hours) for four days. The increase in urinary excretion rate of mercury for both drugs was dependent on the pretreatment rate. DMSA induced a threefold increase in mercury excretion compared with a twofold increase with NAP. Blood mercury concentrations remained low. Neuropsychological testing showed that both drugs reduced hostility. Of the 23 patients, a possible adverse drug reaction was noted in eight on NAP and two on DMSA. Due to the long half-life of mercury (31 to 100 days} chelator therapy may be useful even when administered late. Urinary and not blood mercury concentrations should be used to determine response. Based on increased efficacy and less toxicity, DMSA is superior to NAP.
0
Cyanide Does Not Produce a Hemoglobin Oxygen Saturation Gap
SC Curry, HC Patrick, GR Bond, AH Hall / Samaritan Regional Poison Center, Departments of Medical Toxicology and Medicine, Good Samaritan Medical Center, Phoenix, Arizona; University of Colorado, Denver Toxins that produce abnormal hemoglobin pigments incapable of carrying oxygen (eg, methemoglobin, carboxyhemoglobin) cause lower oxygen saturations of hemoglobin (%sat) than would be predicted based on erythrocytic 2,3-DPG levels, body temperature, and blood pH. This %sat gap can be determined by comparing the difference between the %sat calculated from Po~, pH, and temperature by blood gas instruments and that measured by co-oximetry. Arterial blood has a normal %sat gap of 1% to 3%, while venous blood has a normal %sat gap of 5% to 6% in critically ill patients. Without providing appropriate references, several sources state that during cyanide {CN) poisoning significant amounts of CN bind to ferrous hemoglobin to form cyanhemoglobin, a pigment incapable of carrying oxygen. A resulting %gap of more than 5% has been suggested to be a clue for the diagnosis of CN poisoning, although such has never been reported. We performed in vitro studies where the %sat gap in buffered arterial or venous blood was compared with the same sample containing either 6, 12, or 25 mg/L CN. Cooximetry was performed on co-oximeters available in hospitals in the US (Instrument Laboratories and Radiometer). Calculated %sat was calculated by a Radiometer blood gas instrument utilizing a standard formula. The %sat gap in control samples was low (< 2.2%} and did not differ from those containing CN. There was also no meaningful difference in Po2, Pco2, pH, total hemoglobin, methemoglobin, or carboxyhemoglobin measurements on these instruments. If significant amounts of CN do bind to ferrous heme to form cyanhemoglobin as has been suggested {without supporting evidence}, a %sat gap will not be detectable on instrumentation currently utilized by hospitals in this country.
EmergencyMedicine
631/31
7
Flumazenil and Seizures
D Seger / Vanderbilt University School of Medicine, Section of Surgical Sciences, Division of Trauma, Nashville, Tennessee Flumazenil, a specific benzodiazepine (BZDP) antagonist, is a safe and effective means of reversing central nervous system depressant effects of BZDP. However, clinical trials indicated that reversal of BZDP activity in mixed intoxications with tricyclic antidepressants present may induce seizures. The seizure potential of flumazenil in the presence of tricyclic antidepressants was addressed in an animal model. Twelve pigs {mean weight, 18.7 _+ 4.3 kg) were anesthetized with halothane and nitrous oxide, intubated, and mechanically ventilated. A continuous infusion of nortriptyline was administered until the QRS complex widened to 120 ms. The pigs were divided into three groups of four. In group 1, 15 mg/kg of diazepam was intravenously administered, followed ten minutes later by 5 mg/kg flumazenil. In group 2, 5 mg/kg flumazenil was the sole drug administered. No seizures were observed in group 1 or 2. In group 3, 15 mg/kg diazepam was administered. One animal in this group had seizures. Although the groups are small, these preliminary data indicate that flumazenil does not induce seizures in the presence of tricyclic antidepressants.
8
Fatal Outcome Following Carbon Monoxide Exposure in Pregnancy; A Prospective MulUcenter Study
G Koren, T Sharav, the collaborative group. The Motherisk Program, The Hospital for Sick Children, Toronto, Canada Carbon monoxide (CO) exposure in pregnancy has been reported in more than 45 cases of severe poisoning, mainly with matemal coma, to cause fetal death or permanent central nervous system damage. However, most cases of CO poisoning are not of grades 46, but rather 1-2, without loss of maternal consciousness. No information on fetal outcome after mild-to-moderate CO poisoning has been reported, and therefore counseling of the affected family during pregnancy was not possible. In this multicenter study we have prospectively collected 40 cases, of whom fetal outcome is known in 32, with follow-up of at least one year. These cases were caused by malfunction of furnaces (19), water heaters {six}, and car fumes {seven}. All 25 pregnancies {two sets of twins} with grade 1-2 poisoning resulted in physically and developmentally normal babies up to 1 year of age. Conversely, three of five grade 4-5 poisoning resulted in serious adverse outcome (one maternal and fetal death, one fetal death, and one cerebral palsy with computed tomography scan consistent with severe asphyxia despite uneventful delivery} (P < .001 in Fisher's exact test). An additional woman with grade 5 chose to terminate pregnancy based on information given to her in Motherisk. The two cases of normal outcome after grade 4-5 pois0ning were treated with hyperbaric oxygen whereas adverse fetal effects followed high-flow oxygen. Birth weight was not affected by the time of exposure during gestation. Our data suggest that grades 1-2 CO poisoning are not associated with major fetal damage, whereas following grades 4-5 the likelihood of fetal damage is high and the family should consider termination of pregnancy.
19:6June 1990
Annals of
9
2,3-Dimercaptosuccinic Acid (DMSA) Versus N.AcetyI.Penicillamine (NAP) for the Treatment of Elemental Mercury Toxicity
R Bluhm, RG Bobbitt, JF Bonfiglio, RA Branch, C Sarzen, L Welch, AJJ Wood, AJ Heath / Departments of Medicine and Psychiatry, Vanderbilt University, Nashville, Tennessee Thirty-five patients exposed to elemental mercury vapor during an industrial accident were followed for more than six months. Respiratory symptoms developed within a few days of exposure. Dysuria and ejaculatory pain were noted in six patients. Central nervous system symptoms of headache, memory impairment, and hostility persisted for months. Twenty-three patients were chelated. Twelve were admitted between 73 and 116 days after exposure for a comparative study of DMSA {30 mg/kg/day} and NAP {250 mg every six hours) for four days. The increase in urinary excretion rate of mercury for both drugs was dependent on the pretreatment rate. DMSA induced a threefold increase in mercury excretion compared with a twofold increase with NAP. Blood mercury concentrations remained low. Neuropsychological testing showed that both drugs reduced hostility. Of the 23 patients, a possible adverse drug reaction was noted in eight on NAP and two on DMSA. Due to the long half-life of mercury (31 to 100 days} chelator therapy may be useful even when administered late. Urinary and not blood mercury concentrations should be used to determine response. Based on increased efficacy and less toxicity, DMSA is superior to NAP.
0
Cyanide Does Not Produce a Hemoglobin Oxygen Saturation Gap
SC Curry, HC Patrick, GR Bond, AH Hall / Samaritan Regional Poison Center, Departments of Medical Toxicology and Medicine, Good Samaritan Medical Center, Phoenix, Arizona; University of Colorado, Denver Toxins that produce abnormal hemoglobin pigments incapable of carrying oxygen (eg, methemoglobin, carboxyhemoglobin) cause lower oxygen saturations of hemoglobin (%sat) than would be predicted based on erythrocytic 2,3-DPG levels, body temperature, and blood pH. This %sat gap can be determined by comparing the difference between the %sat calculated from Po~, pH, and temperature by blood gas instruments and that measured by co-oximetry. Arterial blood has a normal %sat gap of 1% to 3%, while venous blood has a normal %sat gap of 5% to 6% in critically ill patients. Without providing appropriate references, several sources state that during cyanide {CN) poisoning significant amounts of CN bind to ferrous hemoglobin to form cyanhemoglobin, a pigment incapable of carrying oxygen. A resulting %gap of more than 5% has been suggested to be a clue for the diagnosis of CN poisoning, although such has never been reported. We performed in vitro studies where the %sat gap in buffered arterial or venous blood was compared with the same sample containing either 6, 12, or 25 mg/L CN. Cooximetry was performed on co-oximeters available in hospitals in the US (Instrument Laboratories and Radiometer). Calculated %sat was calculated by a Radiometer blood gas instrument utilizing a standard formula. The %sat gap in control samples was low (< 2.2%} and did not differ from those containing CN. There was also no meaningful difference in Po2, Pco2, pH, total hemoglobin, methemoglobin, or carboxyhemoglobin measurements on these instruments. If significant amounts of CN do bind to ferrous heme to form cyanhemoglobin as has been suggested {without supporting evidence}, a %sat gap will not be detectable on instrumentation currently utilized by hospitals in this country.
EmergencyMedicine
631/31